Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common tick-borne infection in the United States with more than 20,000 cases reported annually since 2002. Of the available strategies to prevent Lyme disease, only vaccination with a recombinant outer surface protein A and antibiotic chemoprophylaxis of Ixodes scapularis tick bites with single-dose doxycycline have been shown to decrease the incidence of human cases. However, the Lyme vaccine is no longer marketed. In June 2003, authorities from the United States Public Health Services at the Centers for Disease Control and Prevention suggested that single-dose doxycycline be considered as an option for the prevention of Lyme disease after an I. scapularis tick bite (Hayes EB, Piesman J. How can we prevent Lyme disease. N Engl J Med 2003 June 12:348:2424-30). A practical limitation of using doxycycline is that the drug is not available over-the-counter; an antibiotic prescription is required and the medication must be obtained within 72 hours of tick removal for the treatment to be effective. In addition, doxycycline is only recommended for patients bitten by I. scapularis ticks that are engorged with blood, an assessment that requires skill and can only be done if the tick has been saved and is relatively intact. Further, doxycycline is contraindicated in young children and pregnant or lactating women. A variety of topical antimicrobials are in wide general usage for treatment of common conditions. These preparations are well accepted and safe. An animal study demonstrated that application of certain topical antimicrobial preparations was highly efficacious in preventing disseminated Borrelia burgdorferi infection after a tick bite, but unfortunately this study did not test antibiotic formulations approved for use on humans. The purpose of the current proposal is to investigate the efficacy of a topical antibiotic preparation suitable for use in humans in a mouse model. If successful, these studies would have highly relevant public health implications and should result in future human trials to test the efficacy and safety of topical antimicrobial therapy in patients at risk for Lyme disease after an Ixodes scapularis tick bite. [unreadable] [unreadable] [unreadable]